Adrenomedullin production in fibroblasts: Its possible function as a growth regulator of Swiss 3T3 cells

Yoshitaka Isumi, Naoto Minamino, Takeshi Katafuchi, Masanori Yoshioka, Tetsuo Tsuji, Kenji Kangawa, Hisayuki Matsuo

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

In addition to endothelial cells and vascular smooth muscle cells, we demonstrated that adrenomedullin (AM) is synthesized and secreted from fibroblasts, Swiss 3T3, Hs68, and NHLF cells, in a native and biologically active form. Synthesis and secretion of AM from these fibroblasts was regulated by inflammatory cytokines, such as tumor necrosis factor and interleukin-1, lipopolysaccharide, growth and differentiation factors, and hormones in a manner similar to that of vascular smooth muscle cells and endothelial cells. Tumor necrosis factor-α, interleukin-1β, and dexamethasone elevated AM secretion, whereas transforming growth factor-β1 and interferon-γ suppressed it in these three fibroblasts. Swiss 3T3 cells were shown to express receptors specific for AM by both cAMP production and receptor binding assay, and AM was found to stimulate DNA synthesis of quiescent cells through the cAMP-mediated pathway. AM secreted from Swiss 3T3 cells was also confirmed to augment cAMP production and DNA synthesis in the cells themselves. These effects were inhibited by a neutralizing monoclonal antibody against AM. These findings raise the possibility that AM functions as a growth regulator in the case of Swiss 3T3 cells. As AM receptors are widely distributed, AM secreted from fibroblast may play a role as a local regulator in mesenchymal cells of inflammatory or wounded regions.

Original languageEnglish (US)
Pages (from-to)2552-2563
Number of pages12
JournalEndocrinology
Volume139
Issue number5
StatePublished - 1998

Fingerprint

Swiss 3T3 Cells
Adrenomedullin
Fibroblasts
Growth
Adrenomedullin Receptors
Interleukin-1
Vascular Smooth Muscle
Smooth Muscle Myocytes
Endothelial Cells
Tumor Necrosis Factor-alpha
Cyclic AMP Receptors
Growth Differentiation Factors
DNA
Transforming Growth Factors
Neutralizing Antibodies
Interferons
Dexamethasone
Growth Hormone
Lipopolysaccharides
Monoclonal Antibodies

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Isumi, Y., Minamino, N., Katafuchi, T., Yoshioka, M., Tsuji, T., Kangawa, K., & Matsuo, H. (1998). Adrenomedullin production in fibroblasts: Its possible function as a growth regulator of Swiss 3T3 cells. Endocrinology, 139(5), 2552-2563.

Adrenomedullin production in fibroblasts : Its possible function as a growth regulator of Swiss 3T3 cells. / Isumi, Yoshitaka; Minamino, Naoto; Katafuchi, Takeshi; Yoshioka, Masanori; Tsuji, Tetsuo; Kangawa, Kenji; Matsuo, Hisayuki.

In: Endocrinology, Vol. 139, No. 5, 1998, p. 2552-2563.

Research output: Contribution to journalArticle

Isumi, Y, Minamino, N, Katafuchi, T, Yoshioka, M, Tsuji, T, Kangawa, K & Matsuo, H 1998, 'Adrenomedullin production in fibroblasts: Its possible function as a growth regulator of Swiss 3T3 cells', Endocrinology, vol. 139, no. 5, pp. 2552-2563.
Isumi Y, Minamino N, Katafuchi T, Yoshioka M, Tsuji T, Kangawa K et al. Adrenomedullin production in fibroblasts: Its possible function as a growth regulator of Swiss 3T3 cells. Endocrinology. 1998;139(5):2552-2563.
Isumi, Yoshitaka ; Minamino, Naoto ; Katafuchi, Takeshi ; Yoshioka, Masanori ; Tsuji, Tetsuo ; Kangawa, Kenji ; Matsuo, Hisayuki. / Adrenomedullin production in fibroblasts : Its possible function as a growth regulator of Swiss 3T3 cells. In: Endocrinology. 1998 ; Vol. 139, No. 5. pp. 2552-2563.
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